Pub Date : 2023-12-14DOI: 10.3390/biophysica3040045
Anders Brahme, Yvonne Lorat
Most ionizing radiation produces δ-rays of ≈1 keV that can impart MGy doses to 100 nm3 volumes of DNA. These events can produce severe dual double-strand breaks (DDSBs) on nucleosomes, particularly in dense heterochromatic DNA. This is the most common multiply damaged site, and their probabilities determine the biological effectiveness of different types of radiation. We discuss their frequency, effect on cell survival, DNA repair, and imaging by gold nanoparticle tracers and electron microscopy. This new and valuable nanometer resolution information can be used for determining the optimal tumor cure by maximizing therapeutic effects on tumors and minimizing therapeutic effects on normal tissues. The production of DDSBs makes it important to deliver a rather high dose and LET to the tumor (>2.5 Gy/Fr) and at the same time reach approximately 1.8–2.3 Gy of the lowest possible LET per fraction in TP53 intact normal tissues at risk. Therefore, their intrinsic low-dose hyper-sensitivity (LDHS)-related optimal daily fractionation window is utilized. Before full p53 activation of NHEJ and HR repair at ≈½ Gy, the low-dose apoptosis (LDA) and LDHS minimize normal tissue mutation probabilities. Ion therapy should thus ideally produce the lowest possible LET in normal tissues to avoid elevated DDSBs. Helium to boron ions can achieve this with higher-LET Bragg peaks, producing increased tumor DDSB densities. Interestingly, the highest probability of complication-free cure with boron or heavier ions requires a low LET round-up for the last 10–15 GyE, thereby steepening the dose response and further minimizing normal tissue damage. In conclusion, the new high-resolution DSB and DDSB diagnostic methods, and the new more accurate DNA-repair-based radiation biology, have been combined to increase our understanding of what is clinically important in curative radiation therapy. In fact, we must understand that we already passed the region of optimal LET and need to go back one step rather than forward, with oxygen being contemplated. As seen by the high overkill and severely high LET in the distal tumor and the increased LET to normal tissues (reminding of neutrons or neon ions), it is therefore preferable to use lithium–boron ions or combine carbon with an optimal 10–15 GyE photon, electron, or perhaps even a proton round-up, thus allowing optimized, fractionated, curative, almost complication-free treatments with photons, electrons, and light ions, introducing a real paradigm shift in curative radiation therapy with a potential 5 GyE tumor boost, 25% increase in complication-free cure and apoptotic–senescent Bragg Peak molecular light ion radiation therapy.
大多数电离辐射会产生≈1 keV 的 δ 射线，可对 100 nm3 体积的 DNA 产生 MGy 剂量。这些事件可在核小体上产生严重的双链断裂（DDSB），尤其是在密集的异染色质 DNA 中。这是最常见的多重损伤部位，其发生概率决定了不同类型辐射的生物有效性。我们将讨论它们的频率、对细胞存活的影响、DNA 修复以及金纳米粒子示踪剂和电子显微镜成像。这种新的、有价值的纳米分辨率信息可用于确定最佳的肿瘤治疗方法，最大限度地提高对肿瘤的治疗效果，同时最大限度地降低对正常组织的治疗效果。DDSBs 的产生使得向肿瘤提供相当高的剂量和 LET（>2.5 Gy/Fr），同时在 TP53 完整的受威胁正常组织中达到每部分约 1.8-2.3 Gy 的最低 LET 变得非常重要。因此，利用了其内在的低剂量高敏感性（LDHS）相关的最佳日分馏窗口。在 p53 完全激活 NHEJ 和 HR 修复（≈½ Gy）之前，低剂量凋亡（LDA）和 LDHS 可将正常组织的突变概率降至最低。因此，离子疗法最好能在正常组织中产生尽可能低的 LET，以避免 DDSB 的升高。氦到硼离子可以通过更高的 LET 布拉格峰来实现这一目标，从而增加肿瘤的 DDSB 密度。有趣的是，使用硼或更重的离子实现无并发症治愈的可能性最大，这需要在最后 10-15 GyE 采用低 LET 循环，从而使剂量反应陡峭化，进一步将正常组织损伤降至最低。总之，新的高分辨率 DSB 和 DDSB 诊断方法与新的更精确的基于 DNA 修复的放射生物学相结合，加深了我们对治疗性放射治疗的临床重要性的理解。事实上，我们必须明白，我们已经越过了最佳 LET 区域，需要后退一步，而不是向前迈进，目前正在考虑使用氧气。从远端肿瘤的高杀伤力和严重的高LET以及正常组织的LET增加（让人联想到中子或氖离子）可以看出，因此最好使用锂硼离子或将碳与最佳的10-15 GyE光子、电子或甚至质子辐照结合起来，从而实现优化的分次、根治性、近乎复杂的放射治疗、这样就可以利用光子、电子和光离子进行优化的、分次的、治疗性的、几乎无并发症的治疗，为治疗性放射治疗带来真正的范式转变，有可能提高肿瘤治疗效果 5 GyE，将无并发症治愈率提高 25%，并实现凋亡-衰减-布拉格峰分子光离子放射治疗。
{"title":"Dual Nucleosomal Double-Strand Breaks Are the Key Effectors of Curative Radiation Therapy","authors":"Anders Brahme, Yvonne Lorat","doi":"10.3390/biophysica3040045","DOIUrl":"https://doi.org/10.3390/biophysica3040045","url":null,"abstract":"Most ionizing radiation produces δ-rays of ≈1 keV that can impart MGy doses to 100 nm3 volumes of DNA. These events can produce severe dual double-strand breaks (DDSBs) on nucleosomes, particularly in dense heterochromatic DNA. This is the most common multiply damaged site, and their probabilities determine the biological effectiveness of different types of radiation. We discuss their frequency, effect on cell survival, DNA repair, and imaging by gold nanoparticle tracers and electron microscopy. This new and valuable nanometer resolution information can be used for determining the optimal tumor cure by maximizing therapeutic effects on tumors and minimizing therapeutic effects on normal tissues. The production of DDSBs makes it important to deliver a rather high dose and LET to the tumor (>2.5 Gy/Fr) and at the same time reach approximately 1.8–2.3 Gy of the lowest possible LET per fraction in TP53 intact normal tissues at risk. Therefore, their intrinsic low-dose hyper-sensitivity (LDHS)-related optimal daily fractionation window is utilized. Before full p53 activation of NHEJ and HR repair at ≈½ Gy, the low-dose apoptosis (LDA) and LDHS minimize normal tissue mutation probabilities. Ion therapy should thus ideally produce the lowest possible LET in normal tissues to avoid elevated DDSBs. Helium to boron ions can achieve this with higher-LET Bragg peaks, producing increased tumor DDSB densities. Interestingly, the highest probability of complication-free cure with boron or heavier ions requires a low LET round-up for the last 10–15 GyE, thereby steepening the dose response and further minimizing normal tissue damage. In conclusion, the new high-resolution DSB and DDSB diagnostic methods, and the new more accurate DNA-repair-based radiation biology, have been combined to increase our understanding of what is clinically important in curative radiation therapy. In fact, we must understand that we already passed the region of optimal LET and need to go back one step rather than forward, with oxygen being contemplated. As seen by the high overkill and severely high LET in the distal tumor and the increased LET to normal tissues (reminding of neutrons or neon ions), it is therefore preferable to use lithium–boron ions or combine carbon with an optimal 10–15 GyE photon, electron, or perhaps even a proton round-up, thus allowing optimized, fractionated, curative, almost complication-free treatments with photons, electrons, and light ions, introducing a real paradigm shift in curative radiation therapy with a potential 5 GyE tumor boost, 25% increase in complication-free cure and apoptotic–senescent Bragg Peak molecular light ion radiation therapy.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"83 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138971403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-03DOI: 10.3390/biophysica3040044
Bojin Chen, J. Z. Zhang
Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In this study, we employed seven different scoring functions and skeleton clustering to screen the ChemDiv database for 38 compounds, 20 of which originate from the same skeleton structure. The most significant residues from SHMT2 and chemical groups from the inhibitors were identified using ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy), and the binding energy of each residue was quantitatively determined, revealing the essential features of the protein–inhibitor interaction. The two most important contributing residues are TYR105 and TYR106 of the B chain followed by LEU166 and ARG425 of the A chain. The findings will be greatly helpful in developing a thorough comprehension of the binding mechanisms involved in drug–SHMT2 interactions and offer valuable direction for designing more potent inhibitors.
丝氨酸羟甲基转移酶2 (SHMT2)作为癌细胞单碳代谢中丝氨酸/甘氨酸通路的关键催化调节剂，引起了人们的广泛关注。尽管它具有抗癌靶点的潜力，但到目前为止，只有有限数量的抑制剂被发现。在这项研究中，我们使用了7种不同的评分函数和骨架聚类来筛选ChemDiv数据库中的38个化合物，其中20个化合物来自相同的骨架结构。利用ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy)对抑制剂中最显著的SHMT2残基和化学基团进行了鉴定，并定量测定了每个残基的结合能，揭示了蛋白-抑制剂相互作用的基本特征。两个最重要的贡献残基是B链的TYR105和TYR106，其次是A链的LEU166和ARG425。这些发现将极大地有助于深入了解药物- shmt2相互作用的结合机制，并为设计更有效的抑制剂提供有价值的指导。
{"title":"Screening and Analysis of Potential Inhibitors of SHMT2","authors":"Bojin Chen, J. Z. Zhang","doi":"10.3390/biophysica3040044","DOIUrl":"https://doi.org/10.3390/biophysica3040044","url":null,"abstract":"Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In this study, we employed seven different scoring functions and skeleton clustering to screen the ChemDiv database for 38 compounds, 20 of which originate from the same skeleton structure. The most significant residues from SHMT2 and chemical groups from the inhibitors were identified using ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy), and the binding energy of each residue was quantitatively determined, revealing the essential features of the protein–inhibitor interaction. The two most important contributing residues are TYR105 and TYR106 of the B chain followed by LEU166 and ARG425 of the A chain. The findings will be greatly helpful in developing a thorough comprehension of the binding mechanisms involved in drug–SHMT2 interactions and offer valuable direction for designing more potent inhibitors.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"55 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138604896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-25DOI: 10.3390/biophysica3040043
Maurizio Sabbatini, Valentina Bonetto, Valeria Magnelli, C. Lorusso, Francesco Dondero, Maria Angela Masini
Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.
{"title":"Microgravity as an Anti-Metastatic Agent in an In Vitro Glioma Model","authors":"Maurizio Sabbatini, Valentina Bonetto, Valeria Magnelli, C. Lorusso, Francesco Dondero, Maria Angela Masini","doi":"10.3390/biophysica3040043","DOIUrl":"https://doi.org/10.3390/biophysica3040043","url":null,"abstract":"Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139238322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-11DOI: 10.3390/biophysica3040042
Bashiyar Almarwani, Yahia Z. Hamada, Nsoki Phambu, Anderson Sunda-Meya
The cell-penetrating peptide (CPP) penetratin (PEN) has garnered attention for its potential to enter tumor cells. However, its translocation mechanism and lack of selectivity remain debated. This study investigated PEN’s insertion into healthy cells (H-) and cancer cells (C-) using micromolar concentrations and various techniques. Raman spectroscopy was used to determine PEN’s location in the lipid bilayer at different lipid-to-peptide ratios. Dynamic light scattering (DLS) and zeta potential analysis were used to measure the lipid–PEN complex’s size and charge. The results showed helical PEN particles directly inserted into C- membranes at a ratio of 110, while aggregated particles stayed on H- surfaces. Raman spectroscopy and scanning electron microscopy confirmed PEN insertion in C- membranes. Zeta potential studies revealed highly negative charges for PEN–C- complexes and neutral charges for PEN–H- complexes at pH 6.8. C- integrity remained unchanged at a ratio of 110. Specific lipid-to-peptide ratios with dipalmitoylphosphatidylserine (DPPS) were crucial for direct insertion. These results provide valuable insights into CPP efficacy for targeted drug delivery in cancer cells, considering membrane composition and lipid-to-peptide ratios.
{"title":"Investigating the Insertion Mechanism of Cell-Penetrating Peptide Penetratin into Cell Membranes: Implications for Targeted Drug Delivery","authors":"Bashiyar Almarwani, Yahia Z. Hamada, Nsoki Phambu, Anderson Sunda-Meya","doi":"10.3390/biophysica3040042","DOIUrl":"https://doi.org/10.3390/biophysica3040042","url":null,"abstract":"The cell-penetrating peptide (CPP) penetratin (PEN) has garnered attention for its potential to enter tumor cells. However, its translocation mechanism and lack of selectivity remain debated. This study investigated PEN’s insertion into healthy cells (H-) and cancer cells (C-) using micromolar concentrations and various techniques. Raman spectroscopy was used to determine PEN’s location in the lipid bilayer at different lipid-to-peptide ratios. Dynamic light scattering (DLS) and zeta potential analysis were used to measure the lipid–PEN complex’s size and charge. The results showed helical PEN particles directly inserted into C- membranes at a ratio of 110, while aggregated particles stayed on H- surfaces. Raman spectroscopy and scanning electron microscopy confirmed PEN insertion in C- membranes. Zeta potential studies revealed highly negative charges for PEN–C- complexes and neutral charges for PEN–H- complexes at pH 6.8. C- integrity remained unchanged at a ratio of 110. Specific lipid-to-peptide ratios with dipalmitoylphosphatidylserine (DPPS) were crucial for direct insertion. These results provide valuable insights into CPP efficacy for targeted drug delivery in cancer cells, considering membrane composition and lipid-to-peptide ratios.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"39 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135086874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-31DOI: 10.3390/biophysica3040041
David Reguera, Pedro J. de Pablo, Nicola G. A. Abrescia, Mauricio G. Mateu, Javier Hernández-Rojas, José R. Castón, Carmen San Martín
Virus particles consist of a protein coat that protects their genetic material and delivers it to the host cell for self-replication. Understanding the interplay between virus structure and function is a requirement for understanding critical processes in the infectious cycle such as entry, uncoating, genome metabolism, capsid assembly, maturation, and propagation. Together with well-established techniques in cell and molecular biology, physical virology has emerged as a rapidly developing field, providing detailed, novel information on the basic principles of virus assembly, disassembly, and dynamics. The Spanish research community contains a good number of groups that apply their knowledge on biology, physics, or chemistry to the study of viruses. Some of these groups got together in 2010 under the umbrella of the Spanish Interdisciplinary Network on Virus Biophysics (BioFiViNet). Thirteen years later, the network remains a fertile ground for interdisciplinary collaborations geared to reveal new aspects on the physical properties of virus particles, their role in regulating the infectious cycle, and their exploitation for the development of virus-based nanotechnology tools. Here, we highlight some achievements of Spanish groups in the field of physical virology.
{"title":"Physical Virology in Spain","authors":"David Reguera, Pedro J. de Pablo, Nicola G. A. Abrescia, Mauricio G. Mateu, Javier Hernández-Rojas, José R. Castón, Carmen San Martín","doi":"10.3390/biophysica3040041","DOIUrl":"https://doi.org/10.3390/biophysica3040041","url":null,"abstract":"Virus particles consist of a protein coat that protects their genetic material and delivers it to the host cell for self-replication. Understanding the interplay between virus structure and function is a requirement for understanding critical processes in the infectious cycle such as entry, uncoating, genome metabolism, capsid assembly, maturation, and propagation. Together with well-established techniques in cell and molecular biology, physical virology has emerged as a rapidly developing field, providing detailed, novel information on the basic principles of virus assembly, disassembly, and dynamics. The Spanish research community contains a good number of groups that apply their knowledge on biology, physics, or chemistry to the study of viruses. Some of these groups got together in 2010 under the umbrella of the Spanish Interdisciplinary Network on Virus Biophysics (BioFiViNet). Thirteen years later, the network remains a fertile ground for interdisciplinary collaborations geared to reveal new aspects on the physical properties of virus particles, their role in regulating the infectious cycle, and their exploitation for the development of virus-based nanotechnology tools. Here, we highlight some achievements of Spanish groups in the field of physical virology.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"37 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135870248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-28DOI: 10.3390/biophysica3040040
Yasith Indigahawela Gamage, Jianjun Pan
Understanding the membrane interactions of the N-terminal 17 residues of the huntingtin protein (HttN) is essential for unraveling its role in cellular processes and its impact on huntingtin misfolding. In this study, we used atomic force microscopy (AFM) to examine the effects of lipid specificity in mediating bilayer perturbations induced by HttN. Across various lipid environments, the peptide consistently induced bilayer disruptions in the form of holes. Notably, our results unveiled that cholesterol enhanced bilayer perturbation induced by HttN, while phosphatidylethanolamine (PE) lipids suppressed hole formation. Furthermore, anionic phosphatidylglycerol (PG) and cardiolipin lipids, along with cholesterol at high concentrations, promoted the formation of double-bilayer patches. This unique structure suggests that the synergy among HttN, anionic lipids, and cholesterol can enhance bilayer fusion, potentially by facilitating lipid intermixing between adjacent bilayers. Additionally, our AFM-based force spectroscopy revealed that HttN enhanced the mechanical stability of lipid bilayers, as evidenced by an elevated bilayer puncture force. These findings illuminate the complex interplay between HttN and lipid membranes and provide useful insights into the role of lipid composition in modulating membrane interactions with the huntingtin protein.
{"title":"Elucidating the Influence of Lipid Composition on Bilayer Perturbations Induced by the N-Terminal Region of the Huntingtin Protein","authors":"Yasith Indigahawela Gamage, Jianjun Pan","doi":"10.3390/biophysica3040040","DOIUrl":"https://doi.org/10.3390/biophysica3040040","url":null,"abstract":"Understanding the membrane interactions of the N-terminal 17 residues of the huntingtin protein (HttN) is essential for unraveling its role in cellular processes and its impact on huntingtin misfolding. In this study, we used atomic force microscopy (AFM) to examine the effects of lipid specificity in mediating bilayer perturbations induced by HttN. Across various lipid environments, the peptide consistently induced bilayer disruptions in the form of holes. Notably, our results unveiled that cholesterol enhanced bilayer perturbation induced by HttN, while phosphatidylethanolamine (PE) lipids suppressed hole formation. Furthermore, anionic phosphatidylglycerol (PG) and cardiolipin lipids, along with cholesterol at high concentrations, promoted the formation of double-bilayer patches. This unique structure suggests that the synergy among HttN, anionic lipids, and cholesterol can enhance bilayer fusion, potentially by facilitating lipid intermixing between adjacent bilayers. Additionally, our AFM-based force spectroscopy revealed that HttN enhanced the mechanical stability of lipid bilayers, as evidenced by an elevated bilayer puncture force. These findings illuminate the complex interplay between HttN and lipid membranes and provide useful insights into the role of lipid composition in modulating membrane interactions with the huntingtin protein.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-26DOI: 10.3390/biophysica3040039
Ishmael Apachigawo, Dhruvil Solanki, Ruth Tate, Himanshi Singh, Mohammad Moshahid Khan, Prabhakar Pradhan
Biological tissues in nature are fractal due to their self-similarity and porosity properties. These properties change with the progress of some diseases, including brain tissue in leading neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Thus, there is an unmet clinical need to develop a tool for accurate and early diagnosis of AD and PD conditions. Although the whole brain tissues in AD and PD have been extensively studied, their local structural alterations at the nano-to-submicron levels have not been explored. In this paper, we measure the local structural alterations in different brain regions of AD and PD patients by measuring their change in fractal dimensions via optical microscopy. Our results show an increase in the fractal dimension value of ~5–10% in the affected regions of the brain tissues relative to their respective controls. For AD cases, the structural alteration is attributed to the aberrant deposition of amyloid beta protein and neurofibrillary tangles in the brain, and for PD, the gradual loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the brain. The work will enhance the further understanding of alterations in the brain structures in AD and PD and its detection.
{"title":"Fractal Dimension Analyses to Detect Alzheimer’s and Parkinson’s Diseases Using Their Thin Brain Tissue Samples via Transmission Optical Microscopy","authors":"Ishmael Apachigawo, Dhruvil Solanki, Ruth Tate, Himanshi Singh, Mohammad Moshahid Khan, Prabhakar Pradhan","doi":"10.3390/biophysica3040039","DOIUrl":"https://doi.org/10.3390/biophysica3040039","url":null,"abstract":"Biological tissues in nature are fractal due to their self-similarity and porosity properties. These properties change with the progress of some diseases, including brain tissue in leading neurological disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Thus, there is an unmet clinical need to develop a tool for accurate and early diagnosis of AD and PD conditions. Although the whole brain tissues in AD and PD have been extensively studied, their local structural alterations at the nano-to-submicron levels have not been explored. In this paper, we measure the local structural alterations in different brain regions of AD and PD patients by measuring their change in fractal dimensions via optical microscopy. Our results show an increase in the fractal dimension value of ~5–10% in the affected regions of the brain tissues relative to their respective controls. For AD cases, the structural alteration is attributed to the aberrant deposition of amyloid beta protein and neurofibrillary tangles in the brain, and for PD, the gradual loss of dopaminergic neurons and abnormal accumulation of α-synuclein in the brain. The work will enhance the further understanding of alterations in the brain structures in AD and PD and its detection.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":"111 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134908793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-27DOI: 10.3390/biophysica3040038
James P. Chambers, Elena T. Wright, Barbara Hunter, Philip Serwer
Phage characterization for research and therapy can involve newly isolated phages propagated in pathogenic bacteria. If so, characterization requires safety-managing the bacteria. In the current study, we adapt a common and inexpensive reagent, PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA), to safety-manage bacteria in 20 min by selectively inactivating the bacteria. No bacterial survivors are observed among >109 bacteria per ml for a representative of both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Bacillus thuringiensis). This procedure causes no detected inactivation of podophage T3, myophage T4 and siphophage 0105phi7-2. Margins of safety for PrimeStore concentration exist for bacterial inactivation and phage non-inactivation. Thus, general applicability is expected. Subsequent dialysis is used to block long-term effects on phages. Nonetheless, comparable tests should be performed for each pathogenic bacterial strain/phage. Electron microscopy of thin sections reveals inactivation-altered bacterial cytoplasm and a non-disintegrated bacterial envelope (ghosts). Ghosting of E. coli includes re-arrangement of the cytoplasm and the release of endotoxin. The activity of the released endotoxin is >99% reduced after subsequent dialysis, which also removes PrimeStore components. Ghosting of B. thuringiensis includes apparent phase separation within the cytoplasm. The primary application envisaged is biophysical and other screening of phages for therapy of infectious disease.
用于研究和治疗的噬菌体表征可涉及在致病菌中繁殖的新分离噬菌体。如果是这样的话，表征就需要对细菌进行安全管理。在目前的研究中，我们采用了一种常见且廉价的试剂PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA)，通过选择性灭活细菌，在20分钟内对细菌进行安全管理。在每毫升109个革兰氏阴性菌(大肠杆菌)和革兰氏阳性菌(苏云金芽孢杆菌)中均未观察到细菌存活。该过程未检测到足噬细胞T3、肌噬细胞T4和虹吸细胞0105phi7-2失活。对于细菌灭活和噬菌体不灭活，PrimeStore浓度存在安全边际。因此，期望具有普遍的适用性。随后的透析用于阻断对噬菌体的长期影响。尽管如此，应对每一种致病菌株/噬菌体进行比较试验。电镜切片显示失活改变的细菌细胞质和未解体的细菌包膜(鬼)。大肠杆菌的鬼影包括细胞质的重新排列和内毒素的释放。在随后的透析后，释放的内毒素的活性降低了99%，这也去除了PrimeStore成分。苏云金芽孢杆菌的鬼影包括细胞质内明显的相分离。设想的主要应用是用于治疗传染病的噬菌体的生物物理和其他筛选。
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Pub Date : 2023-09-11DOI: 10.3390/biophysica3030037
Daniele Funaro
The deciphering of the genetic code takes place through the reading of the nitrogenous bases, which are four in number. In most cases, the bases are taken three by three, thus generating 64 possible combinations with repetition. Each combination (codon) allows for the synthesis of a specific amino acid. Since the latter are only 21 in number, the codon-amino acid conversion table shows a strong redundancy. Countless efforts have been made to understand the true encryption mechanism. Here, we want to add our version, which consists of associating a periodic sound based on three notes to each codon. RNA now becomes a dynamic object and not just a list of static instructions. In addition to a different interpretation of the genetic code, there is also a considerable reduction in redundancy, given that the number of periodic sounds that can be produced with three notes drops to 20 (with the addition of four pure frequencies). Finally, we discuss the possibility of how these sounds can be generated and travel inside the double helix, and possibly emitted as biophotons.
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Pub Date : 2023-09-05DOI: 10.3390/biophysica3030036
Marc Rico-Pasto, F. Ritort
Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We consider cases where Brownian force fluctuations are large, masking the force rips and jumps characteristics of conformational transitions. We compare unfolding and folding data for DNA hairpin systems of loop sizes 4, 8, and 20 and the 110-amino acid protein barnase, finding conditions that facilitate the detection of folding events at low forces where the signal-to-noise ratio is low. In particular, we discuss the role of temperature as a useful parameter to improve the detection of folding transitions in entropically driven processes where folding forces are temperature independent. The force variance approach might be extended to detect the elusive intermediate states in RNA and protein folding.
{"title":"Detecting Molecular Folding from Noise Measurements","authors":"Marc Rico-Pasto, F. Ritort","doi":"10.3390/biophysica3030036","DOIUrl":"https://doi.org/10.3390/biophysica3030036","url":null,"abstract":"Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We consider cases where Brownian force fluctuations are large, masking the force rips and jumps characteristics of conformational transitions. We compare unfolding and folding data for DNA hairpin systems of loop sizes 4, 8, and 20 and the 110-amino acid protein barnase, finding conditions that facilitate the detection of folding events at low forces where the signal-to-noise ratio is low. In particular, we discuss the role of temperature as a useful parameter to improve the detection of folding transitions in entropically driven processes where folding forces are temperature independent. The force variance approach might be extended to detect the elusive intermediate states in RNA and protein folding.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42895803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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